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The effects of ascorbic acid and oxiracetam on scopolamine-induced amnesia in a habituation test in aged mice.

The effects of a nootropic drug, oxiracetam (50-100-200 mg/kg ip), and a potent antioxidant agent, ascorbic acid (62.5-125-250 mg/kg ip), administered alone or in combination, were investigated on scopolamine-induced amnesia in a mouse habituation test. The light-dark aversion test was selected and was carried out in aged mice. Habituation to the test box occurred over a 3-day period, control mice showing a significant between-day increase in the time spent in the dark box, but not in the number of transitions. On Day 4, following post-trial administration over a 3-day period of oxiracetam (50-100 and 200 mg/kg ip) or ascorbic acid (62.5-125 and 250 mg/kg ip), a significant between-day increase in the time spent in the black area, but not in the number of transitions, was found. The combination of oxiracetam (100 mg/kg ip) with ascorbic acid (125 mg/kg ip) produced a similar pattern of results. The acute administration of scopolamine (0.25 mg/kg ip) to mice treated over a 3-day period with vehicle disrupted the habituation response. In mice that had received the 3-day treatment with oxiracetam or ascorbic acid or its combination, scopolamine failed to alter significantly the learning pattern. In conclusion, these data demonstrate that ascorbic acid, alone or in combination with oxiracetam, may prevent experimentally induced amnesia in aged mice.

Aging↗

Scopolamine administered before and after training impairs both contextual and auditory-cue fear conditioning.

When administered before training to 23-day-old Long-Evans rats, scopolamine hydrobromide significantly impaired both contextual and auditory-cue fear conditioning in a dose-dependent manner. Methylscopolamine which does not cross the blood-brain barrier, however, had no effect on either form of conditioned fear. Scopolamine administered up to 3 h after training also impaired both forms of fear conditioning when administered following a single pairing of the auditory cue and shock. When rats received three pairings, however, a posttraining treatment with scopolamine only impaired contextual fear conditioning. These results suggest that central cholinergic systems are involved in the posttrial processes that establish the memory trace for the conditioning experience.

Animals↗

Effects of scopolamine parenteral administration on the electroretinogram, visual evoked potentials, and quantitative electroencephalogram of healthy volunteers.

Single intramuscular doses of scopolamine and matching placebo were administered to young, healthy, and emmetropic volunteers. Electroretinograms and visual evoked potentials (flash and pattern stimuli) were recorded prior to and 30, 90, and 120 min after administration. The effects of scopolamine at the central nervous system level were monitored also by quantitative electroencephalographic methods. Scopolamine reduced the peak-to-peak amplitude of the late components of the flash-evoked potential without affecting latencies. A decrease of the N75 latency and increment of N175 latency of pattern-evoked potentials were observed without any apparent modification of the amplitude values. These changes were not produced by administering topical cyclopentholate. Electroencephalographic effects were apparent with a longer delay after administration than were those on the visual evoked potentials. No significant modification was observed in the electroretinogram under these recording conditions.

Adult↗

Scopolamine and the control of attention in humans.

Recent work with humans and animals has suggested that the cholinergic system plays an important role in the active control of attention. This study was designed to investigate the effects of scopolamine upon subjects' ability to utilize knowledge of the spatial probability bias in a display in the detection of briefly-presented target letters. Results showed a significant interaction between drug condition (scopolamine 0.9 mg versus Placebo) and target location probability, which indicated that detection of targets in high probability locations decreased under the drug, while detection in low probability locations increased. These results offer support for the notion that scopolamine reduces the efficiency of information encoding because it impairs the optimal utilization of attentional resources.

Adult↗

The effects of scopolamine on working memory in healthy young volunteers.

Twenty healthy young adults completed a series of nonverbal and problem solving tasks in a repeated measures design involving placebo and 0.6 mg scopolamine, administered by subcutaneous injection. Subjects completed the test battery under standard presentation conditions and with concurrent articulation, which precludes verbal recoding of test material. Under standard presentation conditions, scopolamine significantly impaired performance on the problem solving task and on tasks of visuo-spatial and spatial memory; memory for abstract shapes was not impaired. Concurrent articulation impaired performance on the shape recognition and interacted with drug treatment on the problem solving task. The results suggest that scopolamine impairs working memory, and that the decrement is at the level of the central executive mechanisms rather than the subsystems which it controls.

Adolescent↗

Reversal of scopolamine-induced amnesia by phosphatidylserine in rats.

Scopolamine (2 mg/kg IP) and propranolol (55 mg/kg IP), given before a single learning trial, reduce retention of a passive avoidance response in rats. Phosphatidylserine, 30-60 mg/kg IP, antagonizes the amnesic effect of scopolamine but not that of propranolol. The retention of the passive avoidance response is not affected by phosphatidylserine given alone. The results indicate that this phospholipid selectively counteracts the action of scopolamine on passive avoidance acquisition, probably via a cholinergic mechanism.

Amnesia↗

Interaction among scopolamine, conditioned stimulus modality, genotype, and either-way avoidance behavior of rats.

Effects of scopolamine were investigated on either-way avoidance in three genetic lines under auditory and visual conditioned stimuli (CS). In the either-way task, the animal has the option to respond in either of the two directions available. In the genetic line selected for high-avoidance the effects of scopolamine were similar with both auditory and visual CS modes. In the genetic line selected for low-avoidance, and in the genetically heterogeneous line, the effects of the drug were different between the auditory and visual CS. It is suggested that scopolamine is more likely to disrupt responsiveness to visual stimuli, which have become less effective in the low-avoidance line during the course of genetic selection.

Animals↗

Cholinergic learning deficits in the marmoset produced by scopolamine and ICV hemicholinium.

Common marmosets (Callithrix jacchus) were trained to perform daily position discrimination learning tasks in a Wisconsin General Test Apparatus. Acetylcholine receptor blockade with scopolamine was found to impair position learning. Testing on the day after scopolamine treatment suggested that a task learnt under scopolamine was not encoded into long term memory. Acetylcholine depletion achieved by the intraventricular injection of hemicholinium 4 h before testing resulted in a profound impairment of position discrimination learning. It is suggested that central acetylcholine depletion in primates may provide a useful model of senile dementia.

Animals↗

Qualitative analysis of scopolamine-induced amnesia.

The neurochemistry of memory remains to be determined. Acetylcholine may be one of the neuotransmitters which mediates memory function, since the anticholinergic drug scopolamine produces amnesia in man. This study of scopolamine-induced memory deficits further defines those cognitive processes which are disrupted. The drug does not diminish attention, as assessed with an auditory vigilance task, or initial signal detection. More complex auditory decoding is affected, however. Scopolamine impairs aspects of initial memory acquisition (e. g., encoding and consolidation) and spontaneous memory retrieval. Retention is unaffected. Precise delineation of the neurochemistry of human memory will require comparative studies of amnesia-producing compounds, systematically examining the neuropsychological processes impaired by each.

Adult↗

The separate and combined effects of scopolamine and nicotine on human information processing.

Previous work in this and another laboratory has shown that nicotine tablets improve the performance of a rapid information processing task and reduce the Stroop effect, whereas scopolamine has the opposite effects. The purpose of this study was to extend these previous findings by determining whether, when administered together, these two drugs have mutually antagonistic effects on task performance. Two experiments are reported, both using within-subjects double-blind Latin Square designs. In the first, six subjects received single and combined doses of scopolamine 1.2 mg and nicotine 1.5 mg, and there was some evidence that the two drugs had mutually antagonistic effects on the rapid information processing task. In the second experiment 12 subjects received the same doses, but rapid information processing testing was carried out over a longer time period and Stroop testing was introduced at the end of the 2.5 h session. Nicotine was found to counteract the depression of performance produced by scopolamine on both the rapid information task and the Stroop test. These results provide further support for the theory that central cholinergic pathways play a major role in human information processing.

Adolescent↗

Spontaneous alternation of body turns and place: differential effects of amylobarbitone, scopolamine and septal lesions.

Sodium amylobarbitone, scopolamine and septal and hippocampal lesions all reduce spontaneous alternation. However, septal lesions appear to reduce alternation of places more than body turns, while the reverse is true for hippocampal lesions. The present experiments tested the effects of amylobarbitone and scopolamine on place and body turn alternation. Medial and lateral septal lesions were also tested. The former block hippocampal theta rhythm but the latter do not. Amylobarbitone (20 mg/kg, IP) reduced alternation of body turns to chance levels when this was present in control animals, but it did not affect alternation of place. Scopolamine (1.2 mg/kg, IP) reduced both body turn alternation and place alternation. Medial septal lesions produced significant perseveration of body turns and produced a non-significant reduction in place alternation. Lateral septal lesions, tested in a small number of animals, did not appear to affect alternation. The treatments thus reduce spontaneous alternation in differing ways which can in part be accounted for in terms of their differing effects on hippocampal theta rhythm.

Amobarbital↗

Scopolamine and adjunctive drinking in rats.

Nine, food-deprived rats were each given daily sessions during which 60 45-mg food pellets were delivered individually at 60-sec intervals, independently of behaviour. Water spouts were available to the animals and the intermittent delivery of food induced high levels of adjunctive drinking. The administration of scopolamine (0.125, 0.25, 0.5, 1.0 mg/kg) produced a dose-related attenuation of this drinking. A dose of physostigmine (0.2 mg/kg) was found to slightly reduce levels of drinking but this dose did not consistently modify the action of scopolamine on this behaviour. Tolerance was found to occur to the action of the highest dose of scopolamine (1.0 mg/kg).

Animals↗

Cardiovascular effects of Atenolol, scopolamine and their combination on healthy men in Finnish sauna baths.

Indicators of cardiovascular strain were studied in 12 healthy young men under the influence of drugs affecting the autonomic nervous system during the course of taking a sauna bath. There were four bath sessions: one without a drug (control) and three with drug pretreatment (Atenolol 50 mg or Scopolamine 0.3 mg or their combination taken orally 2 h before the bath). The time spent in the hot room depended on the subjective rating of heat stress. Its mean duration at a temperature of 88 degrees C (dry bulb) was 22 (range 14-33) min and did not differ significantly among the sessions. In the Atenolol experiment the mean resting heart rate before the bath was significantly lower (P < 0.001, ANOVA of repeated measures) than in the other experiments. The increase in heart rate per minute of heat exposure was significantly lower (P < 0.001) in the Atenolol experiment and higher (P = 0.017) in the Scopolamine experiment than in the other experiments. The systolic blood pressure increased more slowly (P = 0.004) and the diastolic pressure decreased less (P = 0.02) in the Atenolol experiment than in the other experiments. Heart rate and blood pressure returned to their initial levels during the 30-min recovery after the heat exposure. The plasma noradrenaline concentrations increased approximately twofold during all of the bath sessions, whereas the plasma adrenaline and serum thromboxane B2 concentrations showed no consistent alterations. A small oral dose of Scopolamine alone or in combination with Atenolol produced no marked cardiovascular strain in healthy men during a sauna bath.

Administration, Oral↗

Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats.

Using a repeated acquisition procedure in a three-panel runway apparatus, the effects of minaprine on the impairment of working memory produced by scopolamine, ethylcholine aziridinium ion (AF64A) or cerebral ischemia were investigated in rats. Minaprine (3.2-32 mg/kg IP) as well as idebenone (10-100 mg/kg IP) and physostigmine (0.1-0.32 mg/kg IP) dose-dependently reduced the increase of errors (pushes made on the two incorrect panels located at each choice point) induced by 0.56 mg/kg IP scopolamine. Cerebral ischemia for 5 min caused a significant increase of errors in the runway task. Minaprine at 3.2 and 10 mg/kg administered IP immediately after blood recirculation and again 30 min before the runway test conducted 24 h after ischemia, significantly reduced increases in errors expected to occur after 5 min of ischemia. Physostigmine 0.1 mg/kg similarly attenuated the increase in errors in ischemic rats. However, minaprine at doses up to 32 mg/kg IP failed to reduce the increase of errors induced by AF64A 2.5 nmol injected into the dorsal hippocampus. These findings suggest that minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems.

Animals↗

Crossmodal divided attention in rats: effects of chlordiazepoxide and scopolamine.

"Divided attention" is a psychological construct that hinges on assumptions about a fixed finite capacity of subjects to simultaneously process multiple sets of information. A model of a crossmodal divided attention task was developed in rats. Initially, rats were trained consecutively in operant auditory and visual conditional discrimination tasks. The final task consisted of two successive blocks of 20 trials per modality (modality certainty), followed by 60 trials comprising a semi-randomized sequence of stimuli of both modalities (auditory or visual) and qualities (flashing/pulsing or constantly turned on; modality uncertainty). In comparison to unimodal blocks of trials, performance in the mixed condition was assumed to reflect the demands on the parallel processing of two sets of stimulus-response rules. While response accuracy remained unchanged, response latencies were generally longer in the bimodal condition. Administration of scopolamine (0.03, 0.06, 0.1 mg/kg) or chlordiazepoxide (1, 3, 5, 8 mg/kg) dose-dependently increased response latencies. The scopolamine-induced increase in response latencies was greater in the mixed condition. Cost-benefit analyses demonstrated that the absolute divided attention costs (in ms) were generally higher for visual than for auditory stimuli. Both drugs produced qualitatively similar effects; however, scopolamine was more potent in increasing the absolute divided attention costs than chlordiazepoxide. These data are discussed in terms of the validity of this animal paradigm, and of hypotheses about the effects of benzodiazepine receptor agonists and muscarinic antagonists on brain information processing capacity.

Acoustic Stimulation↗

Effects of microinjection of scopolamine into the neostriatum of rats on performance of a food conditioned reflex at different levels of fixation.

Chronic experiments performed on 32 Sprague-Dawley rats using a movement-feeding operant reflex (Skinner box) model showed that microinjection of scopolamine into the neostriatum had effects on this reflex which depended on the stage of learning. In animals with weakly fixed reflexes (prior to reaching the stage of memory consolidation), bilateral microinjection of 0.3 microgram of scopolamine into the caudate nucleus completely inhibited the reflex for a prolonged period of time. When the operant habit was well fixed, bilateral microinjection of the same doses of scopolamine into the neostriatum had no effect on the reflex. These results suggest that the neostriatum cholinergic system is critically involved in forming the motor engram. The cholinergic system of the caudate nucleus either takes no part in realizing the well-fixed conditioned reflex movement response and/or other forebrain structures are involved in the reflex, compensating for the disturbance in neostriatal cholinergic function.

Animals↗

Scopolamine patch reduces postoperative emesis in paediatric patients following strabismus surgery.

Scopolamine patch was evaluated for the prevention of postoperative emesis in 50 children undergoing strabismus surgery. All subjects were premedicated, with none receiving narcotic premedicants. Anaesthesia included controlled ventilation with the use of muscle relaxants, atropine, and halothane. Before operation, the subjects were randomly assigned to one of two groups: a treatment group received a scopolamine patch at a dose of either 0.75 mg or 0.375 mg, and a control group received no patch. Both the incidence and frequency of vomiting in the scopolamine-treated group were significantly (P less than 0.05) lower than in the control group.

Administration, Cutaneous↗

Scopolamine increases prehensile force during object manipulation by reducing palmar sweating and decreasing skin friction.

The aim of this study was to determine whether relatively long-term changes in skin friction induced by a pharmacological blockade of sweat excretion would alter the grip forces applied to objects of a variety of different surface textures and frictions. Five men and three women were asked to lift the vertically mounted armature of a linear motor between the thumb and index finger and to hold it against an opposing force for 2 s. A 1.0-kHz tone indicated to the subject that the manipulandum had been correctly positioned between the upper and lower position limits. The linear motor generated a 2.5-N force tangential to the skin surface simulating an object weighing approximately 250 g. Three different polyamide plastic surfaces (either smooth or etched with 1.0 mm high Braille beads evenly spaced at 2- or 3-mm intervals) contacted the fingers in these experiments. Subjects lifted and held in a precision grip one of the three surfaces for blocks of ten consecutive trials, but the order of presentation of the three different textures was varied to offset the effect of expectancy. On a second block of ten trials the subjects were requested to release the object slowly to measure the ratio of the grip force normal to the grasped surface to the tangential load force at the moment of slip. This ratio or its inverse provided the coefficient of friction or the slip ratio for a particular subject and surface condition. Twelve hours prior to a second recording session all subjects placed transdermal patches of 1.5 mg scopolamine behind each ear to reduce palmar sweating by blocking the muscarinic receptors of exocrine sweat glands. The subjects were re-tested following procedures that were identical to the first session. Scopolamine significantly reduced the friction of the skin on the smooth and 2-mm beaded surfaces, but the friction of the 3-mm beaded texture was unaffected. Scopolamine also caused subjects to increase both the peak and static grip forces for all the textures including the 3-mm beaded surface, suggesting that for two of the three surfaces they were responding to the increased slipperiness of the skin due to reduced sweat production.

Adult↗